Can Ganciclovir and Quercetin‐P188 Ameliorate Cytomegalovirus Induced Hearing Loss?

Abstract

ObjectiveDetermine whether combination therapy with ganciclovir (GCV) and a Quercetin‐P188 solution improves hearing outcomes in a murine cytomegalovirus (CMV) model.MethodsBALB/c mice were infected with murine CMV on postnatal day 3 (p3). Quercetin was solubilized in saline using P188 (QP188). Treatment groups received either GCV, QP188, GCV and QP188, or P188 delivery vehicle BID at 12‐hour intervals via intraperitoneal injection. All treatment groups were treated for 14 days starting at p3. Uninfected controls were treated with the combined regimen, saline or P188 delivery vehicle. Auditory thresholds were assessed using distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) testing at 4, 6, and 8 weeks of age. Temporal bones from separate CMV‐infected groups were harvested at p10, and viral load was determined by quantitative polymerase chain reaction.ResultsCMV‐infected mice receiving combination therapy GCV+QP188 demonstrated statistically significant lower ABR (p < 0.001) and DPOAE thresholds (p < 0.001) compared with mice treated with GCV monotherapy, QP188 monotherapy, and P188 delivery vehicle at 4, 6, and 8 weeks of age. GCV+QP188 combination therapy, GCV monotherapy, and QP188 monotherapy resulted in a nonsignificant reduction in mean viral titers compared to P188 monotherapy (p = 0.08).ConclusionCombining GCV with the excipients quercetin and P188 effectively ameliorated CMV‐induced sensorineural hearing loss in a murine model. This result may be partially explained by a reduction in viral titers in mouse temporal bones that correlate with in vitro studies demonstrating additive antiviral effect in cell culture.Level of EvidenceNA Laryngoscope, 2023

Role of immunometabolism during congenital cytomegalovirus infection

“…A recent report examined the role of novel pharmacological therapies as synergistic combination therapies. Using a murine model of CMV-associated hearing loss, poloxamer 188 (P188) and quercetin were shown to improve hearing outcomes [30] . A mechanism of action proposed to explain this result was an interaction with the mitochondria and antioxidant properties.…”